- Synthesis and spectral properties of cyclopropyl-substituted phosphaalkenes
-
Cyclopropanecarboxylic acid chlorides 5a-d react with tris(trimethylsilyl)phosphane 6 in benzene at -2 deg C to form cyclopropylcarbonyl-bis(trimethylsilyl)phosphanes 7.These products undergo silylic rearrangement at 25 deg C to yield phosphoalkenes 8.Compounds 8a,b,d are formed as mixtures of Z- and E-isomers where the latter predominante.In the case of 8c, the Z-isomer is formed exclusively. - Key words: phosphaalkenes, cyclopropyl-substituted, E/Z-isomerism.
- Kostitsyn, A. B.,Ruzek, H.,Heydt, H.,Regitz, M.,Nefedov, O. M.
-
-
Read Online
- σ-Bond Hydroboration of Cyclopropanes
-
Hydroboration of alkenes is a classical reaction in organic synthesis in which alkenes react with boranes to give alkylboranes with subsequent oxidation resulting in alcohols. The double bond (π-bond) of alkenes can be readily reacted with boranes owing to its high reactivity. However, the single bond (σ-bond) of alkanes has never been reacted. To pursue the development of σ-bond cleavage, we selected cyclopropanes as model substrates since they present a relatively weak σ-bond. Herein, we describe an iridium-catalyzed hydroboration of cyclopropanes, resulting in β-methyl alkylboronates. These unusually branched boronates can be derivatized by oxidation or cross-coupling chemistry, accessing "designer"products that are desired by practitioners of natural product synthesis and medicinal chemistry. Furthermore, mechanistic investigations and theoretical studies revealed the enabling role of the catalyst.
- Arifin,Itami, Kenichiro,Kato, Hiroki,Kobayashi, Chisa,Kondo, Hiroki,Matsushita, Kaoru,Miyamura, Shin,Yamaguchi, Junichiro,Yokogawa, Daisuke
-
supporting information
p. 11306 - 11313
(2020/07/13)
-
- SUBSTITUTED 2-AMINO-PYRAZOLYL-[1,2,4]TRIAZOLO[1,5A] PYRIDINE DERIVATIVES AND USE THEREOF
-
Provided herein are 2-amino-pyrazolyl-[ 1,2,4]triazolo [1,5a]pyridine derivatives. Such compounds are useful, for example, for the treatment and/or prevention of neurodegenerative diseases or disorders such as ophthalmological neurodegenerative disorders. This disclosure also features compositions containing the same as well as methods of using and making the same.
- -
-
Page/Page column 183
(2020/10/27)
-
- BENZETHERS AND ANILINES OF PYRAZOLYL-AMINO-PYRIMIDINYL DERIVATIVES, AND COMPOSITIONS AND METHODS THEREOF
-
Provided is a novel class of orally and/or topically available, selective and potent JAK inhibitors as safe and effective therapeutics against various diseases and disorders. Also provided is pharmaceutical composition of these compounds and methods of th
- -
-
Paragraph 00209
(2020/10/21)
-
- Pd/Cu-Catalyzed Cascade C(sp3)-H Arylation and Intramolecular C-N Coupling: A One-Pot Synthesis of 3,4-2 H-Quinolinone Skeletons
-
In this letter, we successfully explored a cascade Pd/Cu-catalyzed intermolecular C(sp3)-H arylation of amides and intramolecular C-N coupling reaction. This method provides a one-pot strategy to synthesize 3,4-2H-quinolinone with good regioselectivity of C-H arylation and C-N coupling from C-I and C-X bonds from readily available starting materials.
- Xiao, Han-Zhi,Wang, Wen-Shu,Sun, Yu-Song,Luo, Hao,Li, Bo-Wen,Wang, Xiao-Dong,Lin, Wei-Li,Luo, Fei-Xian
-
supporting information
p. 1668 - 1671
(2019/03/11)
-
- Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
-
Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based lead to give 18 (SBI-553), a potent and brain penetrant NTR1 allosteric modulator.
- Pinkerton, Anthony B.,Peddibhotla, Satyamaheshwar,Yamamoto, Fusayo,Slosky, Lauren M.,Bai, Yushi,Maloney, Patrick,Hershberger, Paul,Hedrick, Michael P.,Falter, Bekhi,Ardecky, Robert J.,Smith, Layton H.,Chung, Thomas D. Y.,Jackson, Michael R.,Caron, Marc G.,Barak, Lawrence S.
-
p. 8357 - 8363
(2019/09/10)
-
- COMBINATION TREATMENTS COMPRISING IMIDAZOPYRAZINONES FOR THE TREATMENT OF PSYCHIATRIC AND/OR COGNITIVE DISORDERS
-
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of psychiatric and/or cognitive disorders such as for example Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, narcolepsy, schizophrenia, cognitive impairment or cognitive impairment associated with schizophrenia (CIAS). Separate aspects of the invention are directed to the combined use of said compounds for the treatment of psychiatric and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of psychiatric and/or cognitive disorders.
- -
-
Page/Page column 73-74
(2018/05/24)
-
- COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF IMIDAZOPYRAZINONES
-
The present invention provides combination treatments comprising administration of compounds that are PDE1 enzyme inhibitors and other compounds useful in the treatment of neurodegenerative disorders such as for example Alzheimer's Disease, Parkinson's Disease or Huntington's Disease. Separate aspects of the invention are directed to the combined use of said compounds for the treatment of neurodegenerative and/or cognitive disorders. The present invention also provides pharmaceutical compositions comprising said PDE1 enzyme inhibitors together with other compounds useful in the treatment of neurodegenerative disorders.
- -
-
Page/Page column 76-77
(2018/05/24)
-
- Synthesis and biological evaluation of new berberine derivatives as cancer immunotherapy agents through targeting IDO1
-
To discover small-molecule cancer immunotherapy candidates through targeting Indoleamine 2,3-dioxygenase 1 (IDO1), twenty–five new berberine (BBR) derivatives defined with substituents on position 3 or 9 were synthesized and examined for repression of IFN-γ-induced IDO1 promoter activities. Structure–activity relationship (SAR) indicated that large volume groups at the 9-position might be beneficial for potency. Among them, compounds 2f, 2i, 2n, 2o and 8b exhibited increased activities, with inhibition rate of 71–90% compared with BBR. Their effects on IDO1 expression were further confirmed by protein level as well. Furthermore, compounds 2i and 2n exhibited anticancer activity by enhancing the specific lysis of NK cells to A549 through IDO1, but not cytotoxicity. Preliminary mechanism revealed that both of them inhibited IFN-γ-induced IDO1 expression through activating AMPK and subsequent inhibition of STAT1 phosphorylation. Therefore, compounds 2i and 2n have been selected as IDO1 modulators for small-molecule cancer immunotherapy for next investigation.
- Wang, Yan-Xiang,Pang, Wei-Qiang,Zeng, Qing-Xuan,Deng, Zhe-Song,Fan, Tian-Yun,Jiang, Jian-Dong,Deng, Hong-Bin,Song, Dan-Qing
-
p. 1858 - 1868
(2017/11/17)
-
- BENZOAZEPINE ANALOGS AS INHIBITING AGENTS FOR BRUTON'S TYROSINE KINASE
-
Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, and methods for their production and compounds of formula (I) for use in treating a disease responsive to the inhibition of Bruton's tyrosine.
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-
Page/Page column 130; 135
(2018/11/10)
-
- Thioamide-Directed Cobalt(III)-Catalyzed Selective Amidation of C(sp3)?H Bonds
-
A mild, oxidant-free, and selective Cp*CoIII-catalyzed amidation of thioamides with robust dioxazolone amidating agents via C(sp3)?H bond activation to generate the desired amidated products is reported. The method is efficient and allows for the C?H amidation of a wide range of functionalized thioamides with aryl-, heteroaryl-, and alkyl-substituted dioxazolones under the Cp*CoIII-catalyzed conditions. The observed regioselectivity towards primary C(sp3)?H activation is supported by computational studies and the cyclometalation is proposed to proceed by means of an external carboxylate-assisted concerted metalation/deprotonation mechanism. The reported method is a rare example of the use of a directing group other than the commonly used pyridine and quinolone classes for Cp*CoIII-catalyzed C(sp3)?H functionalization and the first to exploit thioamides.
- Tan, Peng Wen,Mak, Adrian M.,Sullivan, Michael B.,Dixon, Darren J.,Seayad, Jayasree
-
supporting information
p. 16550 - 16554
(2017/12/07)
-
- IMIDAZOPYRAZINONES AS PDE1 INHIBITORS
-
The present invention provides imidazopyrazinones as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.
- -
-
Page/Page column 74; 75
(2016/11/17)
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- Copper(II)/Silver(I)-Catalyzed Sequential Alkynylation and Annulation of Aliphatic Amides with Alkynyl Carboxylic Acids: Efficient Synthesis of Pyrrolidones
-
A highly efficient protocol for the synthesis of pyrrolidones by the copper-catalyzed alkynylation/annulation of aliphatic amides with alkynyl carboxylic acids is discussed in this paper. A broad range of easily accessible alkynyl carboxylic acids were introduced at the β-methyl group of aliphatic amides with the assistance of an 8-aminoquinolyl auxiliary group via decarboxylation to achieve the subsequent cyclic C-N bond formation within one hour. High selectivity of β-methyl groups over methylene groups was observed, and the extension of this catalytic system to the activation of methylene C-H bonds failed. The substrates with two different groups at the α-position of the aliphatic amides lead to the formation of diastereoisomers which is determined by 1H NMR spectroscopy. The initially produced products with Z-configurations can be easily transformed to the corresponding products with E-configurations by the treatment with dilute p-toluenesulfonic acid after the reaction. This catalytic tandem decarboxylative cyclization provides a new opportunity for the direct functionalization of sp3 C-H bonds.
- Zhang, Jitan,Li, Danyang,Chen, Hui,Wang, Binjie,Liu, Zhanxiang,Zhang, Yuhong
-
supporting information
p. 792 - 807
(2016/03/09)
-
- SUBSTITUTED 5-METHYL-[1, 2, 4] TRIAZOLO [1,5-A) PYRIMIDIN-2-AMINE COMPOUNDS AS PDE2 INHIBITORS
-
The invention provides a chemical entity of Formula (I): (I), wherein R1, R2, R3, and R4, have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by PDE2 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma- dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training; and treating peripheral disorders, including hematological, cardiovascular, gastroenterological, and dermatological disorders.
- -
-
Page/Page column 48-49
(2016/06/01)
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- Ligand-Promoted Borylation of C(sp3)-H Bonds with Palladium(II) Catalysts
-
A quinoline-based ligand effectively promotes the palladium-catalyzed borylation of C(sp3)-H bonds. Primary β-C(sp3)-H bonds in carboxylic acid derivatives as well as secondary C(sp3)-H bonds in a variety of carbocyclic rings, including cyclopropanes, cyclobutanes, cyclopentanes, cyclohexanes, and cycloheptanes, can thus be borylated. This directed borylation method complements existing iridium(I)- and rhodium(I)-catalyzed C-H borylation reactions in terms of scope and operational conditions.
- He, Jian,Jiang, Heng,Takise, Ryosuke,Zhu, Ru-Yi,Chen, Gang,Dai, Hui-Xiong,Dhar, T. G. Murali,Shi, Jun,Zhang, Hao,Cheng, Peter T. W.,Yu, Jin-Quan
-
supporting information
p. 785 - 789
(2016/02/23)
-
- Nickel-catalyzed direct thioetherification of β-C(sp3)-H bonds of aliphatic amides
-
The nickel-catalyzed β-thioetherification of unactivated C(sp3)-H bond of propionamides is established with the assistance of 8-aminoquinoline auxiliary, leading to the β-thio carboxylic acid derivatives. A broad range of functional groups is compatible with this thioetherfication reaction. The process represents the first successful example of metal-catalyzed C-S bond formation from unactivated C(sp3)-H bonds.
- Lin, Cong,Yu, Wenlong,Yao, Jinzhong,Wang, Bingjie,Liu, Zhanxiang,Zhang, Yuhong
-
supporting information
p. 1340 - 1343
(2015/03/14)
-
- Palladium(II)-Catalyzed highly enantioselective C-H arylation of cyclopropylmethylamines
-
C-H arylation via a Pd(II)/Pd(IV) catalytic cycle has been one of the most extensively studied C-H activation reactions since the 1990s. Despite the rapid development of this reaction in the past two decades, an enantioselective version has not been reported to date. Herein, we report a Pd(II)-catalyzed highly enantioselective (up to 99.5% ee) arylation of cyclopropyl C-H bonds with aryl iodides using mono-N-protected amino acid (MPAA) ligands, providing a new route for the preparation of chiral cis-aryl-cyclopropylmethylamines. The enantiocontrol is also shown to override the diastereoselectivity of chiral substrates.
- Chan, Kelvin S. L.,Fu, Hai-Yan,Yu, Jin-Quan
-
supporting information
p. 2042 - 2046
(2015/03/04)
-
- Nickel-catalyzed direct thiolation of unactivated C(sp3)-H bonds with disulfides
-
The first nickel-catalyzed thiolation of unactivated C(sp3)-H bonds with disulfides was described. This transformation uses (dppp)NiCl2 as a catalyst and BINOL as a ligand, which are efficient for the thiolation of β-methyl C(sp
- Yan, Sheng-Yi,Liu, Yue-Jin,Liu, Bin,Liu, Yan-Hua,Zhang, Zhuo-Zhuo,Shi, Bing-Feng
-
supporting information
p. 7341 - 7344
(2015/04/27)
-
- CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS
-
Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.
- -
-
Paragraph 0166; 0167
(2015/07/22)
-
- Cobalt-Catalyzed Cyclization of Aliphatic Amides and Terminal Alkynes with Silver-Cocatalyst
-
A new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes was discovered through a C-H bond functionalization process on unactivated sp3 carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp3)-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. The reaction tolerates a wide variety of functional groups including -F, -Cl, -Br, -CF3, ether, cyclopropane, and thiophene. Both pyridine ligand and aromatic solvent play the important role for the promotion of reactivity. This cobalt-catalyzed cyclization reaction can be successfully extended to a variety of aromatic amides to afford a variety of isoindolinones. Attractive features of this catalytic system include its low cost, easy operation, and convenient access to a wide range of pyrrolidinones and isoindolinones.
- Zhang, Jitan,Chen, Hui,Lin, Cong,Liu, Zhanxiang,Wang, Chen,Zhang, Yuhong
-
supporting information
p. 12990 - 12996
(2015/10/28)
-
- SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
-
Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
- -
-
Paragraph 00629
(2016/04/26)
-
- CYCLOPROPANECARBOXAMIDO-SUBSTITUTE AROMATIC COMPOUNDS AS ANTI-TUMOR AGENTS
-
Provided are cyclopropanecarboxamido-substituted aromatic compounds that inhibit protein kinases and their use in anti-tumor area. In particular, tyrosine-kinase inhibitors and Raf-kinase inhibitors as anti-tumor agents, their preparation, pharmaceutical composition, and their use in the treatment of cancer are also provided.
- -
-
Page/Page column 29; 30
(2014/01/17)
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- 1,2,4-TRIAZOL-5-ONES AND ANALOGS EXHIBITING ANTI-CANCER AND ANTI-PROLIFERATIVE ACTIVITIES
-
Described are compounds of Formula I which find utility in the treatment of cancer, autoimmune diseases and metabolic bone disorders through inhibition of c-FMS (CSF-lR), c-KIT, and/or PDGFR kinases. These compounds also find utility in the treatment of other mammalian diseases mediated by c-FMS, c-KIT, or PDGFR kinases.
- -
-
Paragraph 0390
(2014/09/29)
-
- Triazolopyridines as selective JAK1 inhibitors: From hit identification to GLPG0634
-
Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified
- Menet, Christel J.,Fletcher, Stephen R.,Van Lommen, Guy,Geney, Raphael,Blanc, Javier,Smits, Koen,Jouannigot, Nolwenn,Deprez, Pierre,Van Der Aar, Ellen M.,Clement-Lacroix, Philippe,Lepescheux, Liên,Galien, René,Vayssiere, Béatrice,Nelles, Luc,Christophe, Thierry,Brys, Reginald,Uhring, Muriel,Ciesielski, Fabrice,Van Rompaey, Luc
-
p. 9323 - 9342
(2015/01/09)
-
- PROCESS FOR THE PREPARATION OF PROLINE DERIVATIVES
-
The present invention relates in part to a process for the preparation of a proline derivative of formula I wherein, R1 is C1-7-alkyl or wherein R4 is selected from the group consisting of C1-7-alkyl, halogen-C1-7-alkyl and phenyl optionally substituted by halogen; R2 is halogen or halogen-C1-7-alkyl; and R3 is selected from the group consisting of hydrogen, halogen, halogen-C1-7-alkyl, C1-7-alkoxy, halogen-C1-7-alkoxy and a 5- or 6-membered heterocyclic ring containing one or two nitrogen atoms, said ring being optionally substituted by C1-7-alkyl or halogen. The proline derivatives of the formula I are preferential inhibitors of the cysteine protease Cathepsin S and are therefore useful to treat metabolic diseases like diabetes, atherosclerosis, abdominal aortic aneurysm, peripheral arterial disease and diabetic nephropathy.
- -
-
Paragraph 0155; 0156
(2013/05/22)
-
- PROCESS FOR THE PREPARATION OF 1-ACYL-4-PHENYLSULFONYLPROLINAMIDE DERIVATIVES AND NEW INTERMEDIATES
-
A novel process for the preparation of proline derivatives of formula (I) wherein,R1 is selected from C1-7-alkyl or from formula (II) wherein R4 is selected from C1-7-alkyl, halogen-C1-7-alkyl or from phenyl which is optionally substituted by halogen; R2 is selected from halogen or halogen-C1-7-alkyl; and R3 is selected from hydrogen, halogen, halogen-C1-7-alkyl, C1-7-alkoxy, halogen-C1-7-alkoxy or from a 5- or 6-membered heterocyclic ring containing one or two nitrogen atoms, the ring which is optionally substituted by C1-7-alkyl or halogen is described. The proline derivatives of the formula I are preferential inhibitors of the cysteine protease Cathepsin S and are therefore useful to treat metabolic diseases like diabetes, atherosclerosis, abdominal aortic aneurysm, peripheral arterial disease and diabetic nephropathy.
- -
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Page/Page column 26
(2013/05/23)
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- SUBSTITUTED BICYCLIC HETEROARYL COMPOUNDS AS mPGES-1 INHIBITORS
-
The present invention relates to bicyclic compounds of formula (I) or pharmaceutically acceptable salt thereof as mPGES-1 inhibitors. These compounds are inhibitors of the microsomal prostaglandin E synthase-1 (m PGES-1) enzyme and are therefore useful in the treatment of pain and/or inflammation from a variety of diseases or conditions, such as asthama, osteoarthritis, rheumatoid arthritis, acute or chronic pain and neurodegenerative diseases. (I)
- -
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Page/Page column 41
(2013/03/28)
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- β-Arylation of carboxamides via iron-catalyzed C(sp3)-H bond activation
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A 2,2-disubstituted propionamide bearing an 8-aminoquinolinyl group as the amide moiety can be arylated at the β-methyl position with an organozinc reagent in the presence of an organic oxidant, a catalytic amount of an iron salt, and a biphosphine ligand at 50 C. Various features of selectivity and reactivity suggest the formation of an organometallic intermediate via rate-determining C-H bond cleavage rather than a free-radical-type reaction pathway.
- Shang, Rui,Ilies, Laurean,Matsumoto, Arimasa,Nakamura, Eiichi
-
supporting information
p. 6030 - 6032,3
(2013/05/22)
-
- SGC STIMULATORS
-
Compounds of Formula (I) are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.
- -
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Page/Page column 241-242
(2012/01/15)
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- Palladium(0)-catalyzed enantioselective C-H arylation of cyclopropanes: Efficient access to functionalized tetrahydroquinolines
-
Activated: The title reaction proceeds efficiently with 1 mol % of palladium and gives tetrahydroquinolines in excellent enantioselectivities (see scheme). The enantiodiscriminating concerted metalation-deprotonation step occurs via a rare seven-membered palladacycle. The cyclopropyl-substituted tetrahydroquinolines can be regioselectively and enantiospecifically reduced to chiral tetrahydrobenzoazepines. Copyright
- Saget, Tanguy,Cramer, Nicolai
-
supporting information
p. 12842 - 12845
(2013/02/22)
-
- Highly regioselective carbonylation of unactivated C(sp3)-H bonds by ruthenium carbonyl
-
The regioselective carbonylation of unactivated C(sp3)-H bonds of aliphatic amides was achieved using Ru3(CO)12 as a catalyst. The presence of a 2-pyridinylmethylamine moiety in the amide is crucial for a successful reaction. The reaction shows a preference for C-H bonds of methyl groups as opposed to methylene C-H bonds and tolerates a variety of functional groups. The stoichiometric reaction of an amide with Ru 3(CO)12 gave a dinuclear ruthenium complex in which the 2-pyridinylmethylamino moiety was coordinated to the ruthenium center in an N,N manner.
- Hasegawa, Nao,Charra, Valentine,Inoue, Satoshi,Fukumoto, Yoshiya,Chatani, Naoto
-
supporting information; experimental part
p. 8070 - 8073
(2011/07/08)
-
- Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes
-
Systematic ligand development has led to the identification of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation of cyclopropanes. A diverse range of organoboron reagents can be used as coupling partners, and the reaction proceeds under mild conditions. These results provide a new retrosynthetic disconnection for the construction of enantioenriched cis-substituted cyclopropanecarboxylic acids.
- Wasa, Masayuki,Engle, Keary M.,Lin, David W.,Yoo, Eun Jeong,Yu, Jin-Quan
-
supporting information; scheme or table
p. 19598 - 19601
(2012/01/17)
-
- ORGANIC COMPOUNDS
-
The present invention relates to a compound of formula (I) (I) or a salt thereof, wherein the substituents are as defined in the description, to compositions and use of the compounds in the treatment of diseases ameloriated by inhibition of phosphatidylinositol 3-kinase.
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Page/Page column 49
(2010/04/06)
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- Pd(ll)-Catalyzed olefination of sp3 C-H bonds
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"Chemical equation presented" The first Pd(II)-catalyzed sp3 C-H olefination reaction has been developed using N-arylamide directing groups. Following olefination, the resulting intermediates were found to undergo rapid 1,4-addition to give the corresponding &-lactams. Notably, this method was effective with substrates containing (-hydrogen atoms and could be applied to effect methylene C-H olefination of cyclopropane substrates.
- Wasa, Masayuki,Engle, Keary M.,Yu, Jin-Quan
-
supporting information; experimental part
p. 3680 - 3681
(2010/05/15)
-
- Pd(II)-catalyzed carbonylation of C(sp3)-H bonds: A new entry to 1,4-dicarbonyl compounds
-
Pd(II)-catalyzed β-C(sp3)-H carbonylation of N-arylamides under CO (1 atm) has been achieved. Following amide-directed C(sp3)-H cleavage and insertion of CO into the resulting [Pd(II)-C(sp3)] bond, intramolecular C-N reductive elimination gave the corresponding succinimides, which could be readily converted to 1,4-dicarbonyl compounds. This method was found to be effective with substrates containing α-hydrogen atoms and could be applied to effect methylene C(sp3)-H carbonylation of cyclopropanes.
- Yoo, Eun Jeong,Wasa, Masayuki,Yu, Jin-Quan
-
supporting information; experimental part
p. 17378 - 17380
(2011/02/24)
-
- 2 -AMINO-PYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS
-
2-Aminopyrimidine derivatives of formula (I), wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine H4 receptor antagonists.
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Page/Page column 61
(2009/07/03)
-
- Organic Compounds
-
The present invention relates to compounds of formula I and its salts, wherein the substituents are as defined in the description, to compositions and use of the compounds in the treatment of diseases ameloriated by inhibition of phosphatidylinositol 3-kinase.
- -
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Page/Page column 52
(2009/07/10)
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- BIPIPERIDINYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT
-
Bipiperidinyl compounds of the formula I, are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. Pharmaceutically acceptable salts and solvates are included as well. The compounds are useful as agonists of the g-protein coupled receptor GPR-119.
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Page/Page column 119-120
(2008/12/07)
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- 2-ALKYLBENZOXAZOLE CARBOXAMIDES AS 5HT3 MODULATORS
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Compounds of formulae I and II: are disclosed as 5-HT3 inhibitors. Those compounds are useful in treating CINV, IBS-D and other diseases and conditions.
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Page/Page column 7
(2008/12/08)
-
- CATALYTICS ASYMMETRIC ACTIVATION OF UNACTIVATED C-H BONDS, AND COMPOUNDS RELATED THERETO
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One aspect of the present invention is directed in part to catalytic and stereoselective functionalization of unactivated C-H bonds of simple organic substrates. The compounds and methods provided herein allow one to control the stereochemistry in a C-H activation step, activate substrates containing α-hydrogens next to the directing group, and remove a directing group under mild conditions. One aspect of the present invention relates to a transition-metal-catalyzed method for selective and asymmetric oxidation of carbons located in a β- or γ-position relative to an auxiliary. Another aspect of the invention relates to the enantiomerically-enriched substrates and the enantiomerically-enriched products formed via said method. In certain embodiments, oxazoline and oxazinone directing groups are used. In addition, the Boc protecting group has been identified as a directing group which does not necessitate removal.
- -
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Page/Page column 76-77
(2010/10/20)
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- Palladium-catalyzed asymmetric iodination of unactivated C-H bonds under mild conditions
-
(Chemical Equation Presented) Specific, asymmetric, and mild: Oxazoline (Oxa), a removable chelating chiral auxiliary, assists in the asymmetric activation of C(sp3)-H bonds at the β position and C(sp 2)-H bonds at the γ position. Pd-(OAc)2 is an effective catalyst for the selective and asymmetric iodination of methyl, cyclopropyl, and aryl groups at room temperature (see formulae).
- Giri, Ramesh,Chen, Xiao,Yu, Jin-Quan
-
p. 2112 - 2115
(2007/10/03)
-
- DERIVATIVES OF 4- (IMIDAZOL-5-YL)-2-(4-SULFOANILINO) PYRIMIDINE WITH CDK INHIBITORY ACTIVITY
-
Compounds of the formula (I): wherein R1, R2, R3, R4, R5 and p are as defined within and a pharmaceutically acceptable salts and in vivo hydrolysable esters are described. Also described are processes for their preparation and their use as medicaments, particularly medicaments for producing a cell cycle inhibitory (anti-cell-proliferation) effect in a warm-blooded animal, such as man.
- -
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Page/Page column 63
(2008/06/13)
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- Synthesis of 2,5-dihydroxy-3-(indol-3-yl)benzoquinones by acid-catalyzed condensation of indoles with 2,5-dichlorobenzoquinone
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Three methods for the conjugate addition of indoles to 2,5-dichlorobenzoquinone have been developed. A wide variety of indoles substituted with halogen, alkyl, alkoxy, and aryl groups participate in anaerobic condensation reactions promoted by HCl, H2SO4, or CH3CO2H. The hydroquinone product is partially oxidized by excess dichlorobenzoquinone and fully converted to the 2,5-dichloro-3-(indol-3-yl)benzoquinone targets by DDQ or Ag2CO3 oxidation. 2,5-Dihydroxy- 3-(indol-3-yl)benzoquinones can be obtained from the dichlorides by alkaline hydrolysis. The rotational characteristics of the biaryl bond created in these reactions have been examined by theoretical and spectroscopic methods.
- Pirrung, Michael C.,Deng, Liu,Li, Zhitao,Park, Kaapjoo
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p. 8374 - 8388
(2007/10/03)
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- Pyrimidine derivatives
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This invention provides novel insecticidally and acaricidally active pyrimidine derivatives of formula (I): and stereoisomers thereof, wherein, R1 is selected from alkyl; alkenyl; alkynyl; haloalkyl; haloalkenyl; and cycloalkyl optionally substituted by a
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- Reaction of Cyclopropanamines with Hypochlorite
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Ethylene was formed in 65percent yield when 1-(1-piperidino)cyclopropanol 6, was treated with hypochlorite.This observation raised the possibility that 1-aminocyclopropanecarboxylic acids (ACCs) could yield ethylene by a mechanism that involves (1) decarboxylation to a 1-aminocyclopropanol, followed by (2) a fragmentation of the carbinolamine to ethylene induced by a hypochlorite equivalent.Although this mechanism could be ruled out only for 1e, no evidence could be found for it in the reactions of other ACCs, 1a-f, with hypochlorite.The fact that 1b-cis-2,3-d2 yieldedonly ethylene-cis-1,2-d2 is consistent with either the mechanism described above or a nitrenium ion mechanism.In the reaction of cyclopropanamines with neutral hypochlorite, ethylene is not the major product.From the primary and secondary amino acids 1a-c, a 3-hydroxypropanenitrile or propanamide, 2a-c, probably the product of a nucleophilic ring-opening step followed by decarboxylation, is formed.Similar products are formed from other cyclopropanamines: 2a from 1g, 2d from 1h, 2e and 2f from 1i, and lactone 5 from 1j.
- Vaidyanathan, Ganesan,Wilson, Joseph W.
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p. 1815 - 1820
(2007/10/02)
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- Novel indolobenzazepine derivatives, useful as tranquilizers
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Certain novel 1,2,3,4,8,9-hexahydro-3-(substituted)pyrido[4',3':2,3]indolo[1,7-ab][1]-benzazepines are useful as minor tranquilizers (anxiolytics) and/or major tranquilizers (antipsychotics). The minor tranquilizers are effective at non-ataxic doses, and are not likely to cause addiction when abused. A representative compound in this class is 3-(cyclopropylmethyl)-1,2,3,4,8,9-hexahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine.
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